Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

被引：307

作者：

Hueffmeier, Ulrike ^{[1
]}

Uebe, Steffen ^{[1
]}

Ekici, Arif B. ^{[1
]}

Bowes, John ^{[2
]}

Giardina, Emiliano ^{[3
,4
]}

Korendowych, Eleanor ^{[5
]}

Juneblad, Kristina ^{[6
]}

Apel, Maria

McManus, Ross ^{[7
]}

Ho, Pauline ^{[2
]}

Bruce, Ian N. ^{[2
]}

Ryan, Anthony W. ^{[7
]}

Behrens, Frank ^{[8
]}

Lascorz, Jesus ^{[1
]}

Boehm, Beate ^{[8
]}

Traupe, Heiko ^{[9
]}

Lohmann, Joerg ^{[10
]}

Gieger, Christian ^{[11
]}

Wichmann, Heinz-Erich ^{[11
,12
,13
]}

Herold, Christine ^{[14
]}

Steffens, Michael ^{[14
]}

Klareskog, Lars ^{[15
]}

Wienker, Thomas F. ^{[14
]}

FitzGerald, Oliver ^{[16
,17
]}

Alenius, Gerd-Marie ^{[6
]}

McHugh, Neil J. ^{[5
,18
]}

Novelli, Giuseppe ^{[3
,4
]}

Burkhardt, Harald ^{[8
]}

Barton, Anne ^{[2
]}

Reis, Andre ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany

[2] Univ Manchester, Arthritis Res UK Epidemiol Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[3] Univ Roma Tor Vergata, Dept Biopathol, Ctr Excellence Genom Risk Assessment Multifactori, Sch Med, Rome, Italy

[4] Fdn PTV Policlin Tor Vergata, Rome, Italy

[5] Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England

[6] Univ Hosp, Dept Publ Hlth & Clin Med, Umea, Sweden

[7] Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland

[8] Goethe Univ Frankfurt, Div Rheumatol, Dept Internal Med 2, Frankfurt, Germany

[9] Univ Munster, Dept Dermatol, D-4400 Munster, Germany

[10] Psoriasis Rehabil Hosp, Bad Bentheim, Germany

[11] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany

[12] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany

[13] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

[14] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany

[15] Karolinska Inst, Stockholm, Sweden

[16] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland

[17] Univ Coll Dublin, Sch Med & Med Sci, St Vincents Univ Hosp, Dept Rheumatol, Dublin 2, Ireland

[18] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

爱尔兰科学基金会; 英国惠康基金;

关键词：

GENES; IL23R; IL12B; ACT1;

D O I：

10.1038/ng.688

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 x 10(-17)). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 x 10(-3)). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 x 10(-20), odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

引用

页码：996 / U118

页数：5

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